The long-term goal of this research program is to understand how eukaryotic DMA replication is regulated during the cell cycle. This problem is central to understanding the mechanisms that control cellular proliferation and maintain genomic stability. Our approach to this problem involves the use of genetic and biochemical methods to identify and characterize proteins involved in initiation of DMA replication and its control in the model organism Schizosaccharomyces pombe. Our major objectives are to characterize the assembly and activation of initiation complexes, to define the biochemical mechanisms involved in the replication checkpoint, and to characterize a DNA replication-dependent DMA damage checkpoint that we have recently discovered. We expect that information obtained in our studies will complement that obtained from the study of the Saccharomyces cerevisiae and will be directly relevant to the control of DNA replication in higher eukaryotes. [unreadable] [unreadable] [unreadable]